Trans-ethnic meta-analysis of genome-wide association studies identifies maternal < i > ITPR1 < /i > as a novel locus influencing fetal growth during sensitive periods in pregnancy

by Fasil Tekola-Ayele, Cuilin Zhang, Jing Wu, Katherine L. Grantz, Mohammad L. Rahman, Deepika Shrestha, Marion Ouidir, Tsegaselassie Workalemahu, Michael Y. Tsai Abnormal fetal growth is a risk factor for infant morbidity and mortality and is associated with cardiometabolic diseases in adults. Genetic influences on fetal growth can vary at different gestation times, but genome-wide association studies have been limited to birthweight. We performedtrans-ethnic genome-wide meta-analyses and fine mapping to identify maternal genetic loci associated with fetal weight estimates obtained from ultrasound measures taken during pregnancy. Data included 1,849 pregnant women from four race/ethnic groups recruited through the NICHD Fetal Growth Studies. We identified a novel genome-wide significant association of rs746039 [G] (ITPR1) with reduced fetal weight from 24 to 33 weeks gestation (P6). Additional tests revealed that the SNP was associated with head circumference (P = 4.85x10-8), but not with abdominal circumference or humerus/femur lengths. Conditional analysis in an independent sample of mother-offspring pairs replicated the findings and showed that the effect was more likely maternal but not fetal. Trans-ethnic approaches successfully narrowed down the haplotype block that contained the 99% credible set of SNPs associated with head circumference. We further demonstrated that decreased placental expression ofITPR1 was correlated with increased placental epigenetic age acceler...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research